Synthesis of Mono- and Diaza-‘Pyridones’ via Stille Coupling of Alkoxystannanes

Abstract

Various alkoxy-substituted heterocyclic stannanes provide access to the corresponding substituted ‘pyridone’ moieties via Stille cross-coupling. Both pyridyl and a series of diazinyl stannanes are prepared, and options for unmasking (via demethylation or debenzylation) of the pyridone unit are evaluated.

Key words

pyridine - heterocyclic stannane - Stille coupling

• References and Notes

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• 18 Representative ¹H NMR Data 2-Methoxy-6-(2-methoxyphenyl)pyridine (19c) ¹H NMR (400 MHz, CDCl₃): δ = 7.97 (dd, J = 7.5, 2.0 Hz, 1 H), 7.61 (t, J = 7.5 Hz, 1 H), 7.55 (dd, J = 7.5, 1.0 Hz, 1 H), 7.37 (ddd, J = 8.5, 7.0, 1.5 Hz, 1 H), 7.09 (td, J = 7.5, 1.0 Hz, 1 H), 7.01 (dd, J = 8.5, 1.0 Hz, 1 H), 6.68 (dd, J = 7.5, 1.0 Hz, 1 H), 4.01 (s, 3 H), 3.89 (s, 3 H). 4-Methoxy-2-(4-methoxyphenyl)pyrimidine (21b) ¹H NMR (400 MHz, CDCl₃): δ = 8.45 (d, J = 5.5 Hz, 1 H), 8.40 (d, J = 9.0 Hz, 2 H), 6.98 (d, J = 9.0 Hz, 2 H), 6.56 (d, J = 5.5 Hz, 1 H), 4.07 (s, 3 H), 3.88 (s, 3 H). 2-(Benzyloxy)-6-(thien-2-yl)pyrazine (24d) ¹H NMR (400 MHz, CDCl₃): δ = 8.53 (br s, 1 H), 8.13 (br s, 1 H), 7.66 (dd, J = 4.0, 1.0 Hz, 1 H), 7.53 (d, J = 7.5 Hz, 2 H), 7.46 (dd, J = 5.0, 1.0 Hz, 1 H), 7.31–7.42 (m, 3 H), 7.14 (dd, J = 5.0, 4.0 Hz, 1 H), 5.48 (s, 2 H). 6-(Thien-2-yl)pyridin-2(1H)-one (27) ¹H NMR (400 MHz, CDCl₃): δ = 12.82 (br s, 1 H), 7.98 (d, J = 3.5 Hz, 1 H), 7.43 (t, J = 8.5 Hz, 1 H), 7.38 (d, J = 5.0 Hz, 1 H), 7.16 (dd, J = 5.0, 3.5 Hz, 1 H), 6.52 (d, J = 8.5 Hz, 2 H). 2-Phenylpyrimidin-4(3H)-one (29) ¹H NMR (400 MHz, CDCl₃): δ = 8.19 (dd, J = 8.0, 1.5 Hz, 2 H), 8.15 (d, J = 6.5 Hz, 1 H), 7.52–7.61 (m, 3 H), 6.46 (d, J = 6.5 Hz, 1 H).